The rise of drug-resistant microorganisms has resulted in increasing numbers of infections that are difficult to treat with existing therapies. Although new antibiotics have been developed, problems such as toxicity and relatively narrow spectrum of activity often limit the utility of such drugs.
1-Deoxy-D-xylulose 5-phosphate (DXP) synthase catalyzes the first step in the non-mammalian isoprenoid biosynthetic pathway (FIG. 1A) to form DXP from pyruvate and D-glyceraldehyde 3-phosphate (D-GAP) in a thiamin diphosphate-dependent manner (FIG. 1A). Its unique structure and mechanism distinguish DXP synthase from its homologs, suggesting it could be pursued as an anti-infective drug target. However, few reports describe development of selective inhibitors of this enzyme.